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Platelet adhesion and aggregation are involved in hemostatic maintenance of vascular tone, regulating blood flow turbidity, and inducing inflammatory immune responses to injury. Platelets have been found to secrete redox gasotransmitters, nitric oxide (NO) and hydrogen sulfide (H2S), to regulate their thrombolytic functions. High concentrations of NO can competitively inhibit oxygen binding to cytochrome c oxidase, suppressing oxidative phosphorylation. Nitric oxide can react with superoxide radicals (O2•–) to form peroxynitrite (ONOO•–), a potent oxidant that can damage mitochondrial electron transport proteins. Conversely, H2S can antagonize the deleterious effects of NO through inhibiting O2•– formation and scavenging ONOO•–. Previous work from our lab has found that platelet activation is primarily dependent on glycolysis, but oxidative phosphorylation plays a secondary role for normal functions. Therefore, we propose the presence of a gasotransmitter-mediated mechanism protecting against spontaneous platelet activation during the induction of ROS/RNS. In this study, DetaNONOate (an NO donor) in conjunction with diallyl disulfide (DADS), a H2S donor, was used to evaluate the potential roles of redox transmitters in platelet metabolism using the Seahorse Extracellular Flux Analyser. Our findings corroborated previous understandings of the mitochondrially toxic effects of NO, as elevated DetaNONOate inhibited oxygen consumption rate (OCR) in a dose-dependent manner, suggesting that electron transport machinery was being suppressed or damaged; this dose-dependence was also found with DADS pre-treatment. Damage was reversed when platelets were pre-treated with DADS prior to DetaNONoate exposure; DADS resulted in increased glycolytic flux, leading to recovery of mitochondrial function. These data demonstrate the platelets’ abilities to compensate for acute damage to oxidative phosphorylation machinery using H2S.